Simmons attended Clemson University, and played for the Clemson Tigers football team. As a freshman in 1995, Simmons earned the starting job at inside linebacker after just five days of practice. He finished the season with 150 tackles, and became the first defensive player ever to be named UPI's national freshman of the year, and received first-team All-Atlantic Coast Conference (ACC) honors. As a sophomore, he set the Tigers' record for tackles in a season (178) en route to being named an All-American, and earning another first-team All-ACC selection.

Simmons became one of the premier players in the nation as a junior, and was recognized as a consensus first-team All-American. He led both Clemson and the ACC in tackles (158) and tackles for loss (25) en route to a third-consecutive first-team All-ACC selection. He also led the Tigers in quarterback sacks (8).